scholarly journals KRAS and NRAS Mutations in Moroccan Patients with Colorectal Cancer

2019 ◽  
pp. 254-259
Author(s):  
Dehbi H ◽  
Ait boujmia OK ◽  
Benayad S ◽  
El Idrissi HH ◽  
Karkouri M
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Nras Mutation ◽  
Kras Mutations ◽  
Activating Mutations ◽  
Oncogenic Mutations ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Colorectal Cancer Patients ◽  
Moroccan Patients

Objective: Activating mutations in the RAS proto-oncogene (KRAS, HRAS and NRAS) play a crucial role in carcinogenesis and drug resistance in many cancers including, colorectal cancer. The aim of the present study was to evaluate the frequencies of KRAS and NRAS oncogenic mutations in Moroccan CRC patients.Patients and methods: In the present study, formalin-fixed paraffin-embedded CRC specimens from 114 Moroccan CRC patients were analyzed. To detect mutations in codons 12, 13 and 61 of the KRAS and NRAS genes, the pyrosequencing technique was used.Results: 114 colorectal cancer patients were included in this study, 64 were males and 50 were females, the primary tumor was the most frequent type (78.1%) and the commonest histological type was ADK (77.2%). KRAS mutation was found in 49 of all CRC patients and the most frequent KRAS mutations were 35G>T, 35G>A and 38G>A. On the other hand NRAS mutation was detected only in 6 patients. No statistically significant relationship between CRC patient’s characteristics and RAS mutations was found.Conclusion: Our results suggest that the KRAS mutation is more frequent among Moroccan patients with CRC, which is in agreement with the most previous studies. Further studies, with a larger number of CRC patients, are needed to confirm our findings.

scholarly journals IMPACT OF KRAS MUTATIONS IN CLINICAL FEATURES IN COLORECTAL CANCER

2020 ◽  
Vol 33 (3) ◽  
Author(s):  
Renato Morato ZANATTO ◽  
Gianni SANTOS ◽  
Júnea Caris OLIVEIRA ◽  
Eduardo Marcucci PRACUCHO ◽  
Adauto José Ferreira NUNES ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Kras Mutation ◽  
Direct Sequencing ◽  
Colorectal Carcinogenesis ◽  
Kras Mutations ◽  
Primary Tumor Site ◽  
Exon 2 ◽  
Metastatic Site ◽  
Colorectal Cancer Patients

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

Prevalence of low-penetrance KRAS (codons 12/13 and 61) and BRAF mutations in metastatic colorectal carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14147-e14147
Author(s):  
Federico Rojo ◽  
Trinidad Caldes ◽  
Sandra Zazo ◽  
Miguel de la Hoya ◽  
Cristina Carames ◽  
...  
Keyword(s):  
Wild Type ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Activating Mutations ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Intracellular Signal ◽  
Polymerase Chain ◽  
Current Guidelines ◽  
Formalin Fixed

e14147 Background: In patients with metastatic colorectal cancer (mCRC), activating mutations within KRAS, which result in EGFR-independent intracellular signal transduction activation, are found in approximately 35-40% of patients with mCRC have been significantly associated with lack of response to cetuximab or panitumumab therapy. Although current guidelines recommend testing for frequent KRAS codons 12/13 mutations, emerging data indicate that additional KRAS and BRAF mutations are also predictive of non-responsiveness to anti-EGFR antibodies in mCRC. This study is aimed to analyze the prevalence of low-penetrance KRAS and BRAF V600 mutations in caucasian mCRC population. Methods: A two-institution retrospective cohort of 1,238 consecutive KRAS wild type mCRC patients previously studied for 7 mutations in codons 12/13 (G12D, G12A, G12V, G12S, G12R, G12C and G13D) by the CE-IVD marked ARMS-scorpion real-time polymerase chain reaction PCR (Therascreen, Qiagen) was assayed by the diagnostic TaqMelt PCR assay cobas KRAS mutation and cobas BRAF V600 mutation tests (Roche), which are designed to detect 19 mutations in KRAS codons 12, 13 and 61 (including G12F, G13C, G13R, G13S, G13A, G13V, G13I, Q61H, Q61K, Q61R, Q61L, Q61E and Q61P) and BRAF V600 (V600E, V600K and V600D) mutations. An additional cohort of 146 KRAS mutated patients by ARMS-scorpion PCR was studied. DNA was obtained by cobas DNA preparation kit from one single 5µm formalin-fixed paraffin-embedded tissue section. Results: In all samples, sufficient DNA was obtained for KRAS and BRAF mutational studies. Among 1238 KRAS codons 12/13 wild-type patients by ARMS-scorpion PCR,166 (13.4%) showed KRAS mutations, 117 (9.5%) in codons 12/13, and 49 (4%) in codon 61. BRAF V600 mutations were detected in 9% cases. In ARMS-scorpion PCR KRAS mutated patients, mutations were confirmed by cobas in all cases. Conclusions: The cobas mutation tests are robust and reproducible assays that, 1) detects a higher incidence (13.4%) of mutations in codons 12, 13, and 61 of the KRAS gene in wild-type mCRC population, 2) a relevant rate of BRAF mutations is present in the same population, and 3) requires a very small amount of tissue.

Awareness of KRAS testing by oncologists and panitumumab use in colorectal cancer patients: A European survey.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 547-547
Author(s):  
Jorg Trojan ◽  
Aliki Taylor ◽  
Jan-Henrik Terwey ◽  
Gerry Downey ◽  
George Kafatos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Wild Type ◽  
Nras Mutation ◽  
Mutation Status ◽  
Kras Status ◽  
Level Of Knowledge ◽  
High Level ◽  
Colorectal Cancer Patients ◽  
Kras Mutation Status

547 Background: Panitumumab (Pmab) is licensed for treatment in metastatic colorectal cancer (mCRC) patients with wild type KRAS mutation status (US) and wild type RAS (KRAS and NRAS) mutation status (most other countries). To resolve uncertainties about KRAS testing, a survey and medical records review (MRR) are being carried out in Europe in three rounds: the first two rounds (2012-2013) evaluated KRAS testing and round 3 is evaluating RAS testing. These studies are specific obligations in Europe for the conditional marketing authorization for Pmab. Here we present results of rounds 1 and 2. Methods: Eligible oncologists were contacted by telephone in nine European countries (France, Germany, Italy, Spain, Czech Republic, Netherlands, Belgium, Denmark, and Sweden). To be eligible, the physician was required to be a practicing oncologist and have prescribed Pmab to mCRC patients. Results: 299 of 301 (99.3%) oncologists participating in the survey were aware of the need to perform KRAS testing prior to first dose of Pmab and 294 (97.7%) were aware of patients’ KRAS mutation status prior to first dose. 283 of 301 (94.0%) did not prescribe Pmab to mCRC patients with mutant or unknown KRAS status. 164 physicians administered Pmab simultaneously with oxaliplatin-containing chemotherapy to patients and 10 (6.1%) to patients with mutant or unknown KRAS status. 306 patients from 79 participating oncologists were included in the MRR. 302 of 306 mCRC patients (98.7%) were tested for KRAS tumor status, known by the oncologist before first dose of Pmab. 299 of 302 patients (99.0%) had wild-type KRAS tumor status. 83 of 85 patients (97.6%) treated with Pmab and oxaliplatin-containing chemotherapy had wild-type KRAS tumor status. 55 of 56 linked pathology laboratories (98.2%) participated in a Quality Assurance scheme; all used a CE marked or otherwise validated KRAS detection method. Conclusions: Results from both studies show a high level of knowledge among oncologists of the need for KRAS testing in mCRC patients prior to treatment with Pmab and the contraindication with oxaliplatin-containing chemotherapy with mutant or unknown KRAS tumour status. The final round of this study evaluating RAS testing in Europe is currently underway.

scholarly journals KRAS Mutation Detection in Paired Frozen and Formalin-Fixed Paraffin-Embedded (FFPE) Colorectal Cancer Tissues

2011 ◽  
Vol 12 (5) ◽  
pp. 3191-3204 ◽  
Author(s):  
Jérome Solassol ◽  
Jeanne Ramos ◽  
Evelyne Crapez ◽  
Majda Saifi ◽  
Alain Mangé ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Mutation Detection ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Cancer Tissues ◽  
Formalin Fixed

scholarly journals Clinical characteristics and prognostic value of the KRAS mutation in Chinese colorectal cancer patients

2021 ◽  
pp. 172460082110171
Author(s):  
Ye Yuan ◽  
Yingting Liu ◽  
Ye Wu ◽  
Junling Zhang ◽  
Chunti Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
High Frequency ◽  
Kras Mutation ◽  
Chinese Patients ◽  
Wild Type ◽  
Kras Mutations ◽  
Exon 2 ◽  
Colorectal Cancer Patients

Background: The KRAS mutations are high-frequency somatic mutations found in colorectal cancer patients from Western and Asian countries however, with the exception of exon 2 of KRAS, other prevalence and prognostic values have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of whole exon mutations of KRAS in Chinese colorectal cancer patients and to investigate their impact on prognosis. Methods: A total of 7189 tumor tissue samples (iCohort) were subjected to next-generation sequencing for detection of KRAS mutations. All pathologic or likely pathologic mutations of KRAS were considered. In addition, clinical features and prognostic dates were collected from 145 patients at The Third Affiliated Hospital of Soochow University, China (sCohort) and used droplet digital™ polymerase chain reaction to detect KRAS mutations. Results: In the iCohort, 2706 patients (37.6%) were confirmed harboring KRAS mutations. The most frequent of these mutations were G12D (32.19%), G12V (17.96%), and G13D (17.59%). In the sCohort, 51 colorectal cancer patients (35.17%) had KRAS mutations, among which KRAS G12D (64.71%), G13D (29.41%), and G14D (3.92%) were high-frequency. The KRAS mutations were associated with shorter median overall survival than wild-type tumors (69 vs. 55 months; HR 1.80; 95% Cl 1.22, 2.64; P=0.0003). In the Cox multivariate analysis, age (HR 1.562; 95% Cl 1.10, 2.22; P=0.013), tumor differentiation (HR 0.417; 95% Cl 0.19, 0.90; P=0.026), and KRAS mutation (HR 1.897; 95% Cl 0.19, 0.90; P=0.001) remained independent predictors of shorter overall survival. Among the common KRAS mutations, G12D was significantly associated with shorter overall survival (HR 2.17; 95% Cl 1.31, 3.58; P < 0.0001) compared with KRAS wild-type patients. Conclusions: Our findings indicate that KRAS genes are frequently mutated, and over 30% harbored the KRAS G12D mutation subtype. We found that the KRAS G12D mutation is associated with inferior survival and is a biomarker of poor prognosis in Chinese patients. Our data emphasize the importance of molecular features in colorectal cancer patients, which could potentially be improved by G12D-specific related inhibitors.

scholarly journals The prevalence of KRAS mutation in colorectal cancer patients in Iranian population: A systematic review and meta-analysis study

2017 ◽  
Vol 4 (10) ◽  
pp. 1693 ◽  
Author(s):  
Mehrdad Payandeh ◽  
Nasrin Amirifard ◽  
Masoud Sadeghi ◽  
Babak Shazad ◽  
Negin Farshchian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peer Review ◽  
Kras Mutation ◽  
Meta Analysis ◽  
Scientific Information ◽  
Geographical Area ◽  
Kras Mutations ◽  
Analysis Study ◽  
Peer Reviewers ◽  
Colorectal Cancer Patients

Colorectal cancer (CRC) is one of the most common cancers in the World that KRAS mutations are considered as a key step in the progression of CRC. This meta-analysis study aimed to evaluate the prevalence of KRAS mutations in CRC patients in Iran. Six online databases including PubMed, Science direct, Scopus, Web of science, Cochran Library, and Scientific Information Database (SID) were searched systematically up to January 2017. A random-effects meta-analysis was used to calculate the estimation of the prevalence of KRAS mutations in CRC patients by the event rate (ER) with 95% confidence interval (95%CI). Out of 82 articles identified from the search, eleven studies included and analyzed for meta-analysis study. The studies included 1814 CRC patients that mean age of the patients was 57.5 years. The pooled ER of the studies for estimation of the prevalence of KRAS mutation in CRC patients was 32.8% (95%CI=28.7-37.3%). The pooled ER of the studies for the prevalence of codon 12 mutation was 72.5% (95%CI=59.8-82.3%) and for codon 13 mutation was 20% (95%CI=14.6-26.7%). The results showed that the prevalence of KRAS mutation in Iran was different with more studies that therefore the geographical area and race can impact on the prevalence of KRAS mutation in CRC patients. Also, codon 12 had the most prevalence among mutant codons, followed by codon 13 that Gly to Asp and Gly to Val were the most mutations in codon 12.   Peer Review Details Peer review method: Single-Blind (Peer-reviewers: 02) Peer-review policy Plagiarism software screening?: Yes Date of Original Submission: 07 September 2017 Date accepted: 02 October 2017 Peer reviewers approved by: Dr. Lili Hami Editor who approved publication: Dr. Phuc Van Pham  

Highly sensitive quantitative detection of circulating tumor DNA in urine and plasma from advanced colorectal cancer patients in aid of early diagnosis of clinically relevant KRAS mutations.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 654-654 ◽  
Author(s):  
Jason C. Poole ◽  
Cecile Rose T. Vibat ◽  
Lucie Benesova ◽  
Barbora Belsanova ◽  
Saege Hancock ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Tumor Tissue ◽  
Advanced Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Plasma Samples ◽  
Kras Mutations ◽  
Clinical Sensitivity ◽  
Colorectal Cancer Patients

654 Background: Acquisition of point mutations in KRAS gene is causally associated with the onset of development of a resistance to anti-EGFR therapy in colorectal cancer. Newly acquired KRAS mutations can be detected in blood plasma months before radiographic detection. The objective of this study was to demonstrate feasibility of an ultrasensitive non-invasive method for detection of KRAS mutations in urine and plasma of patients with advanced colorectal cancer. Methods: Archived, matched urine and plasma samples (stored between 3-5 years prior to ctDNA extraction) from 20 treatment naïve, advanced stage cancer patients with known tumor tissue KRAS mutations determined by an accredited clinical laboratory, were used in a retrospective setting for a blinded concordance study. KRAS status in urine and plasma was compared to that in tumor tissue in order to assess clinical sensitivity of the ctDNA assay. An ultrashort-amplicon (31bp) assay for KRAS mutation enrichment and detection in highly fragmented urinary and plasma ctDNA was developed. The assay detected 1 copy of KRASG12A/C/D/R/S/V or G13D mutant allele in a background of wild-type DNA with a verified analytical sensitivity of 0.007% (7 copies per ~100,000 genome equivalents). Results: In a pilot study of 20 advanced stage colorectal cancer patients, 15 of 16 evaluable archived urine samples (94%) had KRAS mutation that was concordant with tissue biopsy. Of 20 archived plasma samples evaluated, 19 (95%) displayed the KRAS mutation concordant with tumor tissue. Of 16 paired urine and plasma samples, 15 (94%) had concordant KRAS mutation calls. Conclusions: This study demonstrates high clinical sensitivity (≥94%) of concordant KRAS mutation detection between urine, plasma and tissue specimens from advanced colorectal cancer patients. Early detection and monitoring of acquired KRAS mutations in circulating tumor DNA, and in particular urinary ctDNA, opens the possibility of a new paradigm for a truly non-invasive method of individualized care for colorectal cancer patients.

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